The development of specialized blood cells, including platelets, via the hematopoietic system requires the interplay of pluripotent cells found in bone marrow and polypeptide cytokines (5). When a patient's levels of circulating platlets are depleted to less than 150.times.10.sup.9 platlets per liter, a condition known as thrombocytopenia can follow. In general, patients with platelet counts between 20 and 100.times.10.sup.9 per liter are at risk of excessive post traumatic bleeding, while those with platelet counts below 20.times.10.sup.9 may bleed spontaneously. These latter patients are candidates for platelet transfusion with associated immune and viral risk.
The major regulator of circulating levels of platelets in the blood is believed to be the recently cloned cytokine thrombopoietin (TPO), the cognate ligand for the receptor encoded by the c-mpl proto-oncogene (c-Mpl) (1-16). TPO has been determined to have both direct proliferative and differentiative activities on human megakaryocyte progenitors. Furthermore, TPO hastens the restoration of platelet counts following cytoreductive therapies and has been associated with improved survival in certain murine models. Treatment of patients suffering from thrombocytopenia with TPO should have therapeutic importance in augmenting megakaryocytopoiesis and circulating blood platelet numbers. The availability of additional agents, capable of stimulating platelet production would be desirable.